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S Rahbar

Publications and source records attributed to S Rahbar.

At least 37 records · Page 2Linked to original sources
PubMed1988

Haplotype analysis of the human beta-globin gene complex using multiple locus specific oligonucleotide probes.

Three oligonucleotide probes complementary to specific DNA sequences of the six human globin genes (epsilon, G gamma, A gamma, psi beta, delta, beta) were synthesized. The oligonucleotides were used either singly or in combination as hybridization probes to determine the haplotype of the human beta-globin gene cluster employing the four conventionally used restriction endonucleases HincII, HindIII, AvaII, and BamHI, in addition to HpaI. Polymorphism in the epsilon- and psi beta-genes (HincII) can be simultaneously determined with a single probe mixture. One of the probes complementary to both the psi beta- and gamma-genes is useful for determining both HindIII and HincII polymorphisms. The advantages of these probes relative to conventional cDNA probes are discussed.

Base Sequence↗
PubMed1988

Carcinogenicity and haemoglobin synthesis induction by cytidine analogues.

We investigated 5-azacytidine and five of its analogues for: (1) carcinogenicity, in the male Fischer rat; (2) toxicities using changes in rat weights in vivo and a cytotoxicity assay in vitro; and (3) haemoglobin gene expression, using minor haemoglobin synthesis in sheep, mice and rats. 5-Azacytidine was found to be a complete carcinogen. It increased the incidence of testicular tumours as well as non-testicular tumours in rats treated for 12 months. 5-Azacytidine also had hepatic tumour promoting properties and was able to induce transplacental carcinogenesis when administered to pregnant rats on day 21 of timed pregnancies. None of the other 5 analogues that were tested appeared to be carcinogenic in small experiments. All the analogues which are known to have hypomethylating activity were found to be cytotoxic in vitro; the most potent being 5-azacytidine. As judged by decreased rat weight compared to untreated controls, the fluorinated cytidine analogues and 5'-deoxyazacytidine were more toxic than 5-azacytidine. Altered haemoglobin synthesis was seen in rats and DBA/2J mice, but not in sheep. In mice, where the clearest haemoglobin changes were noted, an increase in minor haemoglobin synthesis was found using both high and low doses of 5-azacytidine, and with 5,6-dihydro-5-azacytidine and 5-aza-2'-deoxycytidine. These last two analogues appear to be relatively non-toxic, noncarcinogenic in these experiments, and retain haemoglobin activating properties with a potency similar to that of 5-azacytidine.

Animals↗
PubMed1988

LR16, a compound with potent effects on the oxygen affinity of hemoglobin, on blood cholesterol, and on low density lipoprotein.

2-[4-(3,4-Dichlorophenylureido)phenoxy]-2-methylpropionic acid, LR16, combines with two symmetrically related sites in the central cavity of deoxyhemoglobin, 20 A away from the binding site of 2,3-bisphosphoglycerate, and acts as an allosteric effector synergistic with 2,3-bisphosphoglycerate. LR16 (1 mM) raises P50, the partial pressure of oxygen needed to achieve half-saturation with oxygen of a hemolysate of human hemoglobin, about 50 times more strongly than 1 mM 2,3-bisphosphoglycerate. Oral administration of LR16 (at small doses that produced no ill effects) to rats that were fed a diet rich in cholesterol caused substantial reductions of total serum cholesterol and low density lipoprotein-cholesterol, while high density lipoprotein-cholesterol remained unchanged.

Animals↗
PubMed1987

Fetal hemoglobin gene activation in a phase II study of 5,6-dihydro-5-azacytidine for bronchogenic carcinoma.

5-Azacytidine and several of its analogues are known to inhibit DNA methylation, alter gene expression, and inhibit cell growth. We report a Phase II study in which we investigated the antineoplastic activity of 5,6-dihydro-5-azacytidine and its induction of fetal hemoglobin synthesis when given by a 5-day continuous i.v. infusion of 1650 mg/m2/day that was repeated every 21 days. Fetal hemoglobin was measured in all patients; increased synthesis was found in 13 of the 17, in the absence of clinically significant anemia. Of the four patients who did not develop increased fetal hemoglobin, three had only one cycle of therapy. Fourteen patients with bronchogenic carcinoma were treated, and ten were evaluable for disease response. Five patients had disease stability of 2 or more mo, and five progressed on treatment. Three additional patients with mesothelioma were treated, and the two who were evaluable for disease response had stabilization of their disease. Fifteen of the 17 patients who received 5,6-dihydro-5-azacytidine developed a pleuritic-type chest pain, 12 had abnormal electrocardiograms, and four developed positive anti-nuclear antibodies. No significant hemopoietic, hepatic, or renal toxicities were observed. This study demonstrates that 5,6-dihydro-5-azacytidine in the dose and schedule used has no significant therapeutic activity in the treatment of lung cancer but does possess an unusual spectrum of clinical toxicities as well as the property of inducing fetal hemoglobin synthesis.

Adult↗
PubMed1987

Association of hemoglobin H disease with Hb J-Iran (beta 77 His----Asp): impact on subunit assembly.

A young Iranian female was found to be heterozygous for hemoglobin (Hb) J-Iran (beta 77 His----Asp) in combination with Hb H disease. The proportion of Hb J in the patient's hemolysate was surprisingly high: 65% Hb J, 30% Hb A. Thus, the interaction of a negatively charged beta subunit variant of Hb with alpha-thalassemia leads to a marked increase in the relative amount of the variant Hb within red cells. This observation provides further support for an electrostatic model of Hb subunit assembly.

Globins↗
PubMed1986

Microcytosis in Hodgkin disease associated with unbalanced globin chain synthesis.

A review of 162 patients with Hodgkin disease disclosed 36 with microcytic anemia (mean corpuscular hemoglobin values [MCV] less than 80 fl). Three patients had iron deficiency, and one had beta-thalassemia. Of the remaining 32 patients, 24 had microcytic anemia at the time of diagnosis of Hodgkin disease, and ten, including two patients with this finding initially, developed microcytic anemia in association with recurrence of Hodgkin disease. Seven patients with Hodgkin disease and normal MCV had normal alpha-to-beta-globin chain ratios (1.0 +/- 0.14). Seven patients with Hodgkin disease and MCV less than 80 fl had significantly lower alpha-to-beta chain ratios (0.66 +/- 0.05). Twelve normal controls and four with iron-deficiency anemia and MCV less than 80 fl had normal ratios. Anemia was corrected, and MCV returned to normal in all patients who responded to therapy for Hodgkin disease. In the two patients studied sequentially, abnormal alpha-to-beta-chain ratio was corrected along with the anemia.

Anemia↗
PubMed1986

Discrimination among the transcripts of the allelic human beta-globin genes beta A, beta S and beta C using oligodeoxynucleotide hybridization probes.

Three nonadecadeoxynucleotides complementary to the sense strand of the normal human beta-globin gene, beta A, and to the two allelic genes beta S and beta C were synthesized. The beta S and beta C globin genes both differ from the beta A gene by a single nucleotide substitution in the sequence coding for codon 6. The oligodeoxynucleotides are complementary to the genes in the region of the mutations and are therefore allele-specific. When radiolabeled and used as hybridization probes, the oligodeoxynucleotides are found to hybridize specifically to the mRNA transcribed from each allele.

Alleles↗
PubMed1986

Hemoglobin Hammersmith as the cause of severe hemolytic anemia in a Chinese girl.

Hemoglobin Hammersmith, a rare unstable hemoglobin, was diagnosed in a 4-year-old Chinese girl living in Los Angeles. She presented with the typical manifestations of this disorder, including neonatal hyperbilirubinemia, followed by increasing hepatosplenomegaly, jaundice, bilirubinuria, and a severe hemolytic anemia exacerbated by mild infections. The most prominent manifestations of the peripheral smear were polychromasia, normoblastemia, and basophilic stippling. The diagnosis was confirmed by several techniques.

Amino Acids↗
PubMed1986

Reverse phase high-performance liquid chromatography and secondary ion mass spectrometry. A strategy for identification of ten human hemoglobin variants.

Ten abnormal hemoglobins were detected and characterized in individual cases referred to our laboratory for evaluation of hematological problems. Six of these variants were electrophoretically silent and could be detected by reverse phase high-performance liquid chromatography (HPLC) analysis. HPLC was also used to analyze the tryptic peptides of each individual variant. In most of these variants, secondary ion mass spectra of the mixture of the tryptic peptides could reveal the aberrant peptide and predict possible substitution through the mass difference between the normal and abnormal peptide. The mass spectra of the isolated abnormal peptide generally contained sufficient fragment ions to define the position of the amino acid substitution, obviating the need for lengthy sequencing procedures. Combination of the two techniques.

Amino Acid Sequence↗
PubMed1985

Hemoglobin North Chicago (beta 36 [C2] proline----serine): a new high affinity hemoglobin.

Hemoglobin North Chicago, beta 36 [C2] Pro----Ser is a new high oxygen affinity hemoglobin variant. It was discovered in a 52-year-old male with erythrocytosis since age 20 who had been treated with different regimens for polycythemia vera including several courses of 32P. The variant is electrophoretically silent with normal stability and increased oxygen affinity (P50 16.6 mm Hg at 37 degrees C, pH 7.4). Characterization of the structure of hemoglobin North Chicago involved the use of HPLC, secondary ion mass spectral analysis of the tryptic peptides and conventional fingerprinting. Hemoglobin North Chicago manifested bizarre hydrophobicity of its beta-chains, as demonstrated by reverse phase HPLC and Triton X-100 electrophoresis. This behavior is not expected from the substitution of proline to serine. Proline residue beta 36 [C2] is one of the invariant residues of the beta-chains of all known mammals and most vertebrates. This residue is involved in the alpha 1 beta 2 contacts of hemoglobin molecule and its substitution to serine is possibly associated with conformational changes and alteration of hemoglobin function.

Amino Acid Sequence↗
PubMed1984

A silent hemoglobin variant detected by HPLC: hemoglobin City of Hope beta 69 (E13) Gly----Ser.

A silent hemoglobin variant with substitution of serine for glycine at position 69 of the beta-chain was discovered in a healthy individual. Reverse-phase HPLC was used for globin chain separation and to separate the tryptic peptides of the variant. This variant was undetectable by conventional methods of protein separation such as electrophoresis, isoelectric focusing, and ion-exchange chromatography. This observation demonstrates the potential of reverse-phase HPLC as a tool for the search and detection of neutral substitutions in variants of hemoglobin and other proteins, and its usefulness for screening genetic variations in human populations.

Adult↗
PubMed1984

Iron overload in three generations of a family with hemoglobin Olympia.

Erythrocytosis, increased whole blood oxygen affinity, and iron overload were found in a 37-yr-old man. Electrophoretic techniques to demonstrate a hemoglobin variant showed no abnormality. Structural studies of the hemoglobin from this patient revealed an abnormal hemoglobin previously described as Hemoglobin Olympia, a high-affinity variant. Study of three generations in this family showed increased hepatic iron or iron absorption in some members of all three generations studied. The findings in this family are consistent with an increase in iron absorption due to the consequences of Hemoglobin Olympia and the heterozygous state for hemochromatosis (allele for hemochromatosis associated with HLA-A3, B7) or the presence in the family pedigree of three different alleles for hemochromatosis (alleles for hemochromatosis associated with HLA-A3. B7, HLA-A3, B15, and HLA-A9, B44) with the heterozygous state being manifest with increased iron absorption.

Absorption↗
PubMed1983

Heterogeneous ontogeny of erythropoiesis after bone marrow ablation and allogeneic bone marrow grafting.

Thirty-two patients who underwent bone marrow transplantation for hematologic malignancies were studied for hemoglobin-F as an indicator for fetal erythropoiesis. Two different patterns of response were noted. One group of patients who had an elevated HbF level prior to marrow grafting later showed a marked reactivation of HbF synthesis, whereas the other group of patients who had normal HbF levels prior to transplantation failed to exhibit such an increase. This phenomenon occurred independently of ages of marrow graft donors or recipients, the type of underlying hematologic malignancy, or remission induction therapy prior to preparation for transplantation, pretransplant hemoglobin levels, transfusion with red blood cells, red cell volume, and production of reticulocytes.

Adolescent↗